Background: IL-6 signaling is a key component of inflammatory diseases.Results: Modified DNA aptamers that inhibit IL-6 signaling were discovered and optimized.Conclusion: Modified aptamers are stable in serum and block the interaction of IL-6 with its receptor IL-6Rα.Significance: Modified aptamers are a new class of antagonist with properties potentially suitable for clinical treatment of inflammation.
Background: Traditional aptamers favor polar interactions with protein binding partners.Results: The IL-6·SOMAmer structure reveals an interface rich in hydrophobic interactions that overlap the binding sites of IL-6 receptors.Conclusion: Hydrophobic modifications on DNA scaffolds generate diverse and novel structural motifs.Significance: Synthetic SOMAmers are potent, specific, and chemically versatile ligands with distinct binding properties compared with conventional aptamers.
Several compelling lines of evidence suggest an important influence of genetic variation in susceptibility to Kawasaki disease (KD), an acute vasculitis that causes coronary artery aneurysms in children. We performed a family-based genotyping study to test for association between KD and 58 genes involved in cardiovascular disease and inflammation. By analysis of a cohort of 209 KD trios using the transmission disequilibrium test, we documented the asymmetric transmission of five alleles including the interleukin-4 (IL-4) C(-589)T allele (P=0.03). Asymmetric transmission of the IL-4 C(-589)T was replicated in a second, independent cohort of 60 trios (P=0.05, combined P=0.002). Haplotypes of alleles in IL-4, colony-stimulating factor 2 (CSF2), IL-13, and transcription factor 7 (TCF7), all located in the interleukin gene cluster on 5q31, were also asymmetrically transmitted. The reported associations of KD with atopic dermatitis and allergy, elevated serum IgE levels, eosinophilia, and increased circulating numbers of monocyte/macrophages expressing the low-affinity IgE receptor (FCepsilonR2) may be related to effects of IL-4. Thus, the largest family-based genotyping study of KD patients to date suggests that genetic variation in the IL-4 gene, or regions linked to IL-4, plays an important role in KD pathogenesis and disease susceptibility.
Surgeons must bear in mind the possibility of POIB occurrence, especially in cases undergoing particular types of lobectomy (right middle and lower, left upper, right lower or right middle) accompanied by subcarinal LND and having postoperative respiratory complications. Moreover, in appropriate groups with tumors of the right upper lobe or left upper segment, limited mediastinal LND might allow avoidance of POIB.
ABI ankle-brachial index ACC American College of Cardiology ACS acute coronary syndrome AHA American Heart Association APV averaged peak velocity ARH autosomal recessive hypercholesterolemia AS Agatston score ASO arteriosclerosis obliterans ATP adenosine triphosphate BMIPP β-methyl-p-iodophenyl-pentadecanoic acid BNP B-type natriuretic peptide CABG coronary artery bypass grafting CACS coronary artery calcium score CAD coronary artery disease CANM Canadian Association of Nuclear Medicine CanSCMR Canadian Society of Cardiovascular Magnetic Resonance CAR Canadian Association of Radiologists CCS Canadian Cardiovascular Society CCTA coronary CT angiography CDC Centers for Disease Control and Prevention CFR coronary flow reserve CFVR coronary flow velocity reserve CI confidence interval CKD chronic kidney disease CNCS Canadian Nuclear Cardiology Society CPAP continuous positive airway pressure CT computed tomography CTA computed tomography angiography CTDIvol computed omography dose index volume ▋ 2.2.1 Selection of the Lead System and Recording Time Appropriate ECG recording is essential for making a diagnosis of coronary heart disease. Care should be exercised with regard to selection of the electrodes, leads, paste, and lead system to obtain stable recordings during daily activities. The leads that are most likely to reflect ischemic changes are V5-like leads. In particular, lead CM5 is less affected by body movements and has a good detection rate for ischemic changes. 50 A 2-lead system is commonly used, and the AHA guidelines recommend a combination of leads that approximates leads V1 and V5. 51 For capturing ST elevation in patients with variant angina, vertical leads (II, III, and aVF) and approximations to lead V2 or V3 provide a high diagnostic rate. 52 Both circadian and diurnal (dayto-day) variations may exist in relation to the incidence and duration of myocardial ischemia and the extent of ST changes. However, it is difficult to evaluate the influence of diurnal variation based on 24-hour recording, which means that 48-hour recording is desirable for detecting myocardial ischemia and determining the response to treatment. ▋ 2.2.2 Criteria for ST-Segment Changes The diagnostic significance of persistent ST depression on Holter ECG is not high. Rather, detection and evaluation of transient ST-segment changes is more important. The criteria for ST depression are as follows: (1) horizontal or sagging depression of the ST segment by ≥0.1 mV; (2) reaching maximum ST depression after 1 min; and (3) ST depression of ≥0.1 mV lasting for ≥30-60 s compared with the baseline in a controlled state. 49,53-55 ST depression is measured at 0.08 s after the S or J point, and J-type ST depression is not judged to be ischemic ST depression. 52 When counting the number of ischemic episodes, the definition adopted is that each ischemic interval should last for at least 1 min. 56 The criterion for ST elevation is elevation of the ST segment by ≥0.1 mV lasting for ≥30-60 s in leads without Q waves. 49 In patients with chest pain ...
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.